The synergy of (177)Lu-FAPI-46 with tyrosine kinase inhibitor in a sarcoma patient-derived xenograft mouse model

在肉瘤患者来源的异种移植小鼠模型中,(177)Lu-FAPI-46 与酪氨酸激酶抑制剂具有协同作用

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Abstract

BACKGROUND: Given the heterogeneity and high mortality associated with metastatic soft tissue sarcoma, this study aims to evaluate the therapeutic efficacy of combining (177)Lu-FAPI-46 with Pazopanib against this malignancy. METHODS: Patient-derived xenograft (PDX)-bearing mice were randomly divided into three groups: the control group, the (177)Lu-FAPI-46 monotherapy group, and the (177)Lu-FAPI-46 combined with Pazopanib therapy group. Therapeutic efficacy was regularly monitored. RESULTS: The microPET imaging showed a 0.84-fold decrease in the T/M ratio of 68Ga-FAPI-46 on day 7/8 post combination therapy, while the control group exhibited a 1.23-fold increase. Combination therapy significantly inhibited tumor proliferation, as evidenced by reduced Ki-67 and increased caspase 3 expressions. Notably, there was no significant body weight loss observed in any group. CONCLUSION: This study successfully demonstrated the reduction in FAP expression and suppression of tumor volume in sarcoma PDX following the combination therapy of (177)Lu-FAPI-46 with Pazopanib.

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